CONVERSION OF ANTERIOR LIMB BUD CELLS TO ZPA SIGNALING CELLS IN-VITROAND IN-VIVO

Following a graft of posterior (zone of polarizing activity or ZPA) ce lls into the anterior margin of the developing chick wing bud, anterio r cells are induced to alter their developmental fate and form structu res that are normally composed of posterior cells. When anterior cells are cultured under microdissociation conditions they develop ZPA sign aling ability within 24 hr. ZPA signaling in these cultures is transie nt and once established the level of ZPA signaling declines with time in culture. ZPA signaling in anterior cells is sensitive to treatment with fibroblast growth factor-2 (FGF-2); the development of ZPA signal ing is inhibited when nonsignaling anterior cells are cultured in the presence of FGF-2. Conversely, when anterior cells that have developed ZPA signaling are treated with FGF-2, ZPA signaling levels are mainta ined. Thus, our results suggest that FGF-2 maintains or stabilizes the positional character of anterior (nonsignaling) cells, as well as ant erior ZPA signaling converted cells, and posterior (ZPA signaling) lim b bud cells in vitro (R. Anderson, M. Landry, and K. Muneoka (1993) De velopment 117, 1421-1433). In addition, anterior cells will convert to ZPA signaling cells in vivo following apical ectodermal ridge (AER) r emoval, suggesting that a factor(s) localized to the AER prevents ante rior cells from developing ZPA signaling capability during limb outgro wth. These findings indicate that nonsignaling anterior limb bud cells have the potential to become ZPA signaling cells and that FGF-2, or a related factor, functions in the maintenance of positional states in the developing limb. (C) 1994 Academic Press, Inc.